Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Potential Apoptotic Activities of Hylocereus undatus Peel and Pulp Extracts in MCF-7 and Caco-2 Cancer Cell Lines

There is a huge demand for novel anticancer agents with fewer side effects compared to current therapies. Pitaya, or dragon fruit, is a reservoir of potent anticancer compounds. This research aimed to analyze the phytochemical components of Hylocereus undatus pulp and peel extracts using LC-MS and GC-MS, and to investigate the in vitro effects of both extracts against cancer (breast, MCF-7, and colon, Caco-2) and normal (lung; WI-38 and breast; MCF-10A) cell proliferation using the MTT assay. The apoptosis potential of the anticancer effects was also evaluated using flow cytometry, RT-PCR, and Western blot. The total phenolic and flavonoid contents in the peel extract were significantly higher than those in the pulp extract. Compared to the flavonoid and phenolic acid standards, the LC-MS analysis revealed the presence of nine compounds, which were represented as 84.32 and 5.29 &micro;g/g of the flavonoids and 686.11 and 148.72 &micro;g/g of the phenolic acids in the peel and pulp extracts, respectively. Among the identified compounds, chlorogenic acid, caffeic acid, ferulic acid, and rutin were found at the highest concentration in both plant extracts. Both extracts displayed cytotoxic activity against MCF-7 and Caco-2 cancer cells after 48 h of treatment at IC50 values ranging from 14 to 53 &mu;g/mL with high selective indices against normal WI-38 and MCF-10A cell lines. The increase in apoptosis was revealed by the overexpression of p53, BAX, and caspase-9 and the downregulation of antiapoptotic Bcl-2 mRNA and protein expressions. The results indicate that H. undatus extracts can be a plant source for cancer therapy

Phenolic profile, anti-inflammatory, antinociceptive, anti-ulcerogenic and hepatoprotective activities of Pimenta racemosa leaves

Abstract Background Pimenta racemosa tree has many traditional uses where its leaves are used as herbal tea for treatment of flatulence, gastric disorder, osteoarthritis, colds and fever in addition to its analgesic and anti-inflammatory activities. So, this study aimed to isolate phenolic constituents of 80% aqueous methanol extract (AME) of leaves and evaluate its biological activities. Methods The defatted AME was chromatographed and structures of the isolated compounds were elucidated using UV, NMR spectroscopy and UPLC-ESI-MS analysis. Antioxidant activity was investigated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Anti-inflammatory activity was evaluated using carrageenan - induced paw oedema, while antinociceptive activity was determined by chemical and thermal stimuli. Anti-ulcerogenic effect of AME against gastric damage induced by ethanol in Wister male albino rats was evaluated. Also, hepatoprotective activity was investigated through determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) following oral administration of paracetamol. Both of Anti-ulcerogenic and hepatoprotective activities (125, 250 and 500 mg/kg b.wt.) were supported by histopathological examinations. Results Gallic acid (1), methyl gallate (2), avicularin (3), quercetin 3-O-β-D-arbinopyranoside (4), quercetin 3-O-β-D-glucopyranoside (5), quercetrin (6), cynaroside (7), strictinin (8), castalagin (9), grandinin (10) quercetin (11) and ellagic acid (12) were isolated. AME showed significant radical scavenging activity (SC50 = 4.6 μg/mL), promising anti-inflammatory effect through inhibition of oedema and antinociceptive activity by reduction in number of writhes after acetic acid injection and prolongation of reaction time towards the thermal stimulus. AME reduced the gastric mucosal lesions compared with ethanol control and ranitidine groups, ALT at the three doses and AST only at 125 and 250 mg/kg b.wt., when compared with paracetamol group. The results were confirmed by histopathological studies. Conclusion P. racemosa leaves are rich in phenolic compounds and showed significant biological activities

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2–15.1], 13 J/min [IQR 10–17], and 14 J/min [IQR 11–20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14–1.30) and HD3 (1.38, 95% CI 1.23–1.53), reintubation on HD1 (1.64; 95% CI 1.57–1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18–1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56–2.78) and HD3 (1.76; 95% CI 1.41–2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study.

Background Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. Methods We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5\u201315 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. Findings 15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34\ub75%) underwent appendicectomy. The normal appendicectomy rate was 15\ub79% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0\ub784 (95% CI 0\ub782\u20130\ub786). Applying score cutoffs of 3 points or lower for children aged 5\u201310 years and girls aged 11\u201315 years, and 2 points or lower for boys aged 11\u201315 years, the failure rate was 3\ub73% (95% CI 2\ub70\u20135\ub72; 18 of 539 patients), specificity was 44\ub73% (95% CI 41\ub74\u201347\ub72; 521 of 1176), and positive predictive value was 41\ub74% (38\ub75\u201344\ub74; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72\ub76%, 67\ub74\u201377\ub74) was similar to that of ultrasound scan (75\ub70%, 65\ub73\u201383\ub71). Interpretation The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. Funding None